Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 7 appraisals
Journal of medicinal chemistry
MEG-mod: A Multiview Enhanced Graph Neural Network for Knockdown Efficiency Prediction of Chemically Modified siRNA
Chemical modification is essential for improving the stability and knockdown efficiency of siRNAs. However, the combinatorial complexity of modification types and positions makes rational design difficult. Here, we propose MEG-mod, a deep learning framework for predicting the knockdown efficiency of chemically modified siRNAs. By integrating a literature-reading agent, manual curation, and public database resources, we construct an expanded data set. MEG-mod jointly models sequence context, physicochemical properties, chemical modification features, and duplex structural relationships. A structure-aware Transformer-based graph neural network captures base-pairing and adjacency dependencies within double-stranded siRNAs, while a modification-base fusion module models context-dependent modification effects. MEG-mod outperforms existing methods, achieving a pearson correlation coefficient of 0.9171. The attention mechanism enables interpretable analysis of key modification positions and modification types, and provides recommendations consistent with reported experimental designs. MEG-mod is available as a public web server (https://lmmd.ecust.edu.cn/megmod/), providing a practical tool for prediction and candidate prioritization of chemically modified siRNAs.
13 June 2026
Read appraisal →Neurosurgical review
Short-and long-term responsiveness of deep brain stimulation on motor and cognitive outcomes in GBA vs. Non-GBA parkinson's disease: a systematic review and meta-analysis of observational studies
Deep brain stimulation (DBS) is an established therapy for motor complications in Parkinson's disease (PD). Patients carrying glucocerebrosidase (GBA) mutations exhibit distinct disease trajectories, raising questions regarding potential differences in clinical outcomes following DBS compared with non-carriers. To evaluate short- and long-term motor, medication, and cognitive outcomes following DBS in patients with GBA-PD compared with non-GBA PD. We conducted a systematic review and meta-analysis of studies reporting clinical outcomes in PD patients with and without GBA mutations who underwent DBS and had a minimum follow-up of one year. Random-effects inverse variance models were applied, with subgroup analyses according to GBA status. DBS was associated with significant improvements in motor function in the off-medication state and sustained reductions in levodopa equivalent daily dose in both GBA carriers and non-carriers, with no significant between-group differences. Cognitive performance declined over long-term follow-up in both groups. At five years, greater cognitive decline, assessed using the Mattis Dementia Rating Scale, was observed among GBA-PD mutation carriers compared with non-carriers. Motor improvement and medication reduction following DBS were comparable between PD patients with and without GBA mutations. Over long-term follow-up, greater cognitive decline was observed among GBA-PD carriers.
21 May 2026
Read appraisal →Cerebellum (London, England)
Quantitative Ocular Motor / Vestibular Assessment in Patients with Spinocerebellar Ataxia Type 3 (SCA3, Machado Joseph Disease) - Systematic Review of the Literature
Spinocerebellar ataxia type 3 (SCA3 or Machado-Joseph disease) is the second most common autosomal-dominant hereditary ataxia and often presents with ocular motor and vestibular impairment. The value of ocular motor testing for early disease detection, monitoring disease progression and as a potential treatment biomarker has been acknowledged in several studies. This systematic review aims to summarise the current evidence supporting quantitative eye movement testing in SCA3. Studies reporting on quantitative ocular motor and/or vestibular measurements in SCA3 were searched for in MEDLINE and Embase. Thirty studies reporting on 432 SCA3 patients (including 64 pre-symptomatic carriers) were included. Information on various ocular motor parameters were extracted and correlations with other parameters (including clinical scales, imaging, and genetic testing) were assessed. Ocular motor abnormalities observed comprised (horizontal) pursuit eye-movement (PEM) gain reduction (14/19 patients), saccadic intrusions (principally square-wave jerks (SWJ, 29/45)), gaze-evoked nystagmus (GEN, 65/82), and rebound nystagmus (8/10). Additionally, saccades to target displayed increased latency (13/29), reduced peak velocity (16/49) and dysmetria (33/49). Vestibular deficits measured included vestibulo-ocular reflex (VOR) gain-reductions during quantitative head-impulse testing (qHIT, 117/133) and abnormal responses during caloric irrigation (7/9), impaired visually-enhanced VOR-responses (5/6), and impaired cervical (19/66) and ocular (10/14) vestibular-evoked myogenic-potential testing. In summary, impaired VOR-gains (qHIT), GEN, horizontal PEM-gain decreases, dysmetric saccades, and SWJ were most frequently reported and therefore seem most suitable as potential disease markers. The quantitative ocular motor/vestibular assessment may facilitate early diagnosis, distinction of disease stages and also potentially allow monitoring of disease progression and treatment response.
14 May 2026
Read appraisal →Molecular biology reports
Genetic modulation of pain pathways: toward a new era in pain therapy- a systematic review
Gene therapy represents a new strategy in pain management targeting the causes of pain rather than its symptoms. This review summarizes recent advances across RNA interference (RNAi), viral vector delivery systems, CRISPR/Cas9, gene replacement therapy, and endogenous opioid gene delivery, emphasizing efficacy, safety, and mechanisms of action in pain conditions. RNAi and gene replacement techniques remain powerful tools for reducing pain and improving the quality of life by modulating pain-associated genes. Long-term relief may also be achieved with CRISPR/Cas9 and site-directed delivery using nanoparticle systems. Safety profiles especially with CRISPR/Cas9 remains a concern. A systematic search of Web of Science, Medline, Scopus, and Google Scholar identified 512 records (January 2010-March 2023). Following PRISMA screening, 18 studies met inclusion criteria. These studies evaluated strategies of gene therapy in neuropathy, arthritis, fibromyalgia, and complex regional pain syndrome. The review outlines available options and highlights preclinical findings.
11 May 2026
Read appraisal →Curr Opin Pediatr
Artificial intelligence supported facial feature analysis in medical genetics
PURPOSE OF REVIEW: This review highlights recent developments in the use of machine learning supported facial feature analysis in the context of genetic and syndromic conditions. The review focusses on 2D image-based tools. The 2D images are easily obtained using handheld devices such as mobile phones and are more relevant to general practice than 3D image based systems. RECENT FINDINGS: Different algorithms are used widely in pediatric clinics, medical genetics clinics, for gene variant analysis and in research. Integrated systems combining next-generation phenotyping with next-generation genotyping support a shortened diagnostic odyssey for patients. SUMMARY: Future integration of phenotyping using data available in electronic medical records with genotyping data will likely result in earlier identification of possible genetic conditions.
1 Dec 2025
Read appraisal →Genes (Basel)
The Evolving Role of Artificial Intelligence in Medical Genetics: Advancing Healthcare, Research, and Biosafety Management
The integration of artificial intelligence (AI) with medical genetics is transforming healthcare by addressing the analytical challenges posed by the vast complexity of multi-omics data. This review explores the synergistic convergence of these fields, highlighting AI's transformative role in enhancing diagnostic precision, enabling non-invasive molecular profiling through imaging-genetics, and advancing predictive and personalized medicine via polygenic risk scores and pharmacogenomics. AI is also emerging as a powerful generative tool in therapeutic design, accelerating drug discovery, protein engineering, and precision gene editing. However, this powerful synergy introduces significant ethical, regulatory, and biosecurity challenges, including data privacy, algorithmic bias, and the dual-use risks of AI-enabled genetic engineering. The future envisions a responsible co-evolution, with multimodal AI and the concept of the Digital Twin driving precision medicine, underpinned by interdisciplinary collaboration to ensure fairness, transparency, and societal trust. This article charts the current landscape and proposes actionable directions, emphasizing the need for robust governance to harness AI's potential while mitigating its risks for the benefit of human health.
1 Dec 2025
Read appraisal →Nat Med
Feasibility and clinical utility of expanded genomic newborn screening in the Early Check program
Although genomic sequencing presents groundbreaking newborn screening (NBS) opportunities, critical feasibility and utility questions remain. Here we present initial results from the Early Check program-an observational study assessing the feasibility and clinical utility of genomic NBS in North Carolina. Recruitment was statewide through mailed letters with electronic consent. Genome sequencing with analysis of 169 high actionability genes (plus 29 optional lower actionability genes) was performed using residual NBS dried blood spots. In 8 months, 1,979 newborns were screened, with 50 (2.5%) screen positives. Negative results were returned electronically, positive results by genetic counselors. Twenty-eight results (55%) were true positives, all received anticipatory guidance, surveillance and management recommendations, and referral to specialists as appropriate. We report technical feasibility and preliminary clinical utility finding, along with interpretation and follow-up challenges that hinder public health implementation. We propose standardized terminology to facilitate cross-study comparisons and accurate characterization of genomic NBS outcomes.
1 Nov 2025
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